Hornum Mads, Burton Christopher M, Iversen Martin, Hovind Peter, Hilsted Linda, Feldt-Rasmussen Bo
Department of Nephrology, Division of Lung Transplantation, University of Copenhagen, Copenhagen Ø, Denmark.
Nephrol Dial Transplant. 2007 Dec;22(12):3616-22. doi: 10.1093/ndt/gfm478. Epub 2007 Aug 3.
The nephrotoxity of calcineurin inhibitors in lung-transplanted patients is well described, but previous studies have estimated rather than directly measured glomerular filtration rate (GFR). This study describes the decline of measured GFR in a large cohort of lung-transplanted patients from a national centre, and the correlation between measured and calculated GFR.
All lung-transplanted patients 1992-2004 (n = 390) were included in a longitudinal analysis. Seven patients were excluded due to retransplantation. Pre- and post-transplant parameters included (51)Cr-labelled EDTA clearance (mGFR) and the Cockcroft-Gault calculated clearance (cGFR). Trough cyclosporine levels (C0) and demographic and transplant information were also included in the analysis.
A total of 66959 C0 and serum creatinine and 1945 mGFR measurements pertaining to 383 patients were included in the analysis. Pre-transplant mGFR was significantly lower with respect to recipient age over 60 years; and patients with a referral diagnosis of pulmonary hypertension had a lower mGFR and higher baseline serum creatinine levels than patients with emphysematous disease (P < 0.05). There were linear correlations between log(10) mean interval serum creatinine and log(2) mGFR at all time points pre- and post-transplantation (P < 0.0001, Spearman correlation coefficient = -0.81) and between log(2) cGFR and log(2) mGFR (P < 0.0001, Spearman correlation coefficient = 0.81), however, the agreement between mGFR and cGFR was poor (-2.7 +/- 38.6 ml/min). A simplified repeated measure ANOVA model describing post-transplant GFR over time demonstrated a 54% decline in mGFR within the first 6 months post-transplant. Pre-transplant mGFR was an important determinant of 6 month post-transplantation mGFR. Increasing mean C0, body mass index and early acute renal failure were independent risk factors for a more rapid decline in post-transplant mGFR.
mGFR decreases dramatically during the first 6 months after lung-transplantation. Avoidance of high dose calcineurin inhibition may postpone the onset of post-transplant end-stage renal failure.
钙调神经磷酸酶抑制剂在肺移植患者中的肾毒性已有充分描述，但既往研究是估算而非直接测量肾小球滤过率（GFR）。本研究描述了来自一个国家中心的一大群肺移植患者中实测GFR的下降情况，以及实测GFR与计算所得GFR之间的相关性。
纳入1992年至2004年期间所有肺移植患者（n = 390）进行纵向分析。7例因再次移植被排除。移植前后参数包括（51）铬标记的依地酸清除率（mGFR）和Cockcroft - Gault计算清除率（cGFR）。分析还纳入了环孢素谷浓度（C0）以及人口统计学和移植信息。
分析纳入了383例患者的共计66959次C0和血清肌酐测量值以及1945次mGFR测量值。移植前mGFR在60岁以上受者中显著更低；转诊诊断为肺动脉高压的患者与肺气肿疾病患者相比，mGFR更低且基线血清肌酐水平更高（P < 0.05）。移植前后所有时间点，log(10)平均间隔血清肌酐与log(2) mGFR之间以及log(2) cGFR与log(2) mGFR之间均存在线性相关性（P < 0.0001，Spearman相关系数 = -0.81和0.81），然而，mGFR与cGFR之间的一致性较差（-2.7 ± 38.6 ml/min）。一个描述移植后GFR随时间变化的简化重复测量方差分析模型显示，移植后前6个月mGFR下降了54%。移植前mGFR是移植后6个月mGFR的重要决定因素。平均C0升高、体重指数增加和早期急性肾衰竭是移植后mGFR更快下降的独立危险因素。
肺移植后前6个月mGFR急剧下降。避免高剂量钙调神经磷酸酶抑制可能会推迟移植后终末期肾衰竭的发生。
